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Vaccines, Blood & Biologics

1/31/2007 Filing Meeting Email 2 - RECOTHROM

From: Renshaw, Carolyn

Sent: Wednesday, January 31, 2007 2:30 PM

To: Shields, Mark; Aebersold, Paul; Drews, Roman T; Gallagher, Maryann; Hshieh, Paul; Buehler, Paul (CBER); Kirschbaum, Nancy; Lee, Timothy; Lindsey, Kimberly; White, Janet; Buehler, Paul (CBER)

Cc: Trout, Deborah; Eltermann, John

Subject: RE: 125248/0 Filing Meeting

I recommend filing STN 125248/0 based on the facility and microbiology information in the BLA. However, I have the following issues/comments:

  • ------------------------
    • Action limit of final ------ during consistency lot campaign was ------------. Proposed action limit for future manufacturing is ----------------.
      • During PAI, review historical ------------ results to determine if the action limit is appropriate.
    • -------------------------------------------------------------------------------------------------------. This seems high for a recombinant product. Typically see lower for other products.
  • Endotoxin
    • ---------------------------------------- endotoxin limit is -------------------. -----------------------------------------------------------. This seems rather high although the route of administration may warrant less stringent requirements (topical rather than IV) and also it is a blood component 610/14(b).
  • Environmental Assessment
    • 21 CFR 25.31(e) is quoted as the reason for categorical exclusion. This is only relevant for an IND. They should use 25.31(c) , naturally occurring substance.
  • There is a problem with popped-up stoppers after lyophilization. These vials are discarded but this raises concerns regarding sterility assurance. They have modified the vials and revalidated CC integrity for future lots.
  • Integrity testing of the container/closure for the final bulk was not described.
  • Why is the ----------------------------------------------------------------------------------------------------------------------------?
  • Sterilization and depyrogenation of the CC, equipment, and components is described in the BLA. The descriptions provide some details but the information is still highly summarized.
    • Either ask for executive summary reports or review during the PAI.
  • Actual media fill validation results were not provided. They only described the requirements for performing and passing media fills and stated the media fills had passed.
    • Ask for the summary report or review during the PAI.
  • The moisture specification for final drug product is --------------. Do they have stability data to support the upper limit?
  • Lyophilization validation was described but the actual results were not submitted.
    • Ask for validation summary reports or review during the PAI.

I have requested the following master files:

  • --------------------------------------
  • Two amendments from ---------- regarding the stoppers:
    • --------------------------------------------------------------------------------

The ------------------are out but I will receive them when they are available.

Pre-approval inspection status:

  • Most likely will need three PAIs.
  • Decision will occur this week.
  • Firm is sending production schedules for --------------------------.
  • Most likely will perform a combined inspection with Team Bio for the -------------------. -----------. The participation of Team Bio is unannounced - please do not inform the firm.


Carolyn Renshaw
NLRC, Room 233A

From: Shields, Mark

Sent: Wednesday, January 31, 2007 9:56 AM

To: Shields, Mark; Aebersold, Paul; Drews, Roman T; Gallagher, Maryann; Hshieh, Paul; Buehler, Paul (CBER); Kirschbaum, Nancy; Lee, Timothy; Lindsey, Kimberly; Renshaw, Carolyn; White, Janet; Buehler, Paul (CBER))

Subject: Updated: 125248/0 Filing Meeting

When: Wednesday, January 31, 2007 1:00 PM-2:00 PM (GMT-05:00) Eastern Time (US & Canada).

Where: By email.

The filing meeting will be held by email. Please provide an email that states that this can be filed and share any known problems. Thanks!

Short Summary: New BLA - Thrombin (Recombinant)

Contact FDA

(800) 835-4709
(240) 402-8010
Consumer Affairs Branch (CBER)

Division of Communication and Consumer Affairs

Office of Communication, Outreach and Development

Food and Drug Administration

10903 New Hampshire Avenue

Building 71 Room 3103

Silver Spring, MD 20993-0002

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